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Associations of dietary supplement use with all-cause and cause-specific mortality in patients diagnosed with cancer: a large prospective cohort study in the UK Biobank

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Abstract

Purpose

Despite the increasing popularity of supplement use among the cancer community, the current evidence on its effect on mortality in large studies is inconclusive. This study examined the association of dietary supplement use with mortality risk in a large population-based cohort.

Methods

This prospective cohort study analyzed data from the UK Biobank on participants who were diagnosed with cancer before July 31, 2019 and self-reported whether they had regular intake of dietary supplements (vitamins, minerals, or non-vitamin non-mineral [NVNM] supplements) after cancer diagnosis. The associations between the use of supplements with mortality were analyzed using Cox proportional hazards models, adjusting for confounders (sociodemographic factors, lifestyle and comorbidities).

Results

This analysis included 30,239 participants (mean age: 60.0 years; 61.9% female). Over half (57.8%) were supplement users. At a median follow-up of 11.9 years, 5577 all-cause deaths were registered. A marginal protective effect of supplement use on the risk of all-cause (adjusted hazard ratio [aHR] = 0.95, 95% CI = 0.90–0.99) and cancer (aHR = 0.89, 95% CI = 0.83–0.95) mortality were found, but not the risk of mortality due to other causes. In subgroup analyses, only NVNM dietary supplements were significantly associated with a lower risk of all-cause mortality (aHR = 0.88, 95% CI = 0.83–0.93). Both vitamins (aHR = 0.93, 95% CI = 0.87–0.99) and NVNM dietary supplements (aHR = 0.88, 95% CI = 0.82–0.94) were associated with a modest decrease in cancer mortality which were marginally significant.

Conclusions

This is one of the largest cohort studies that identified the associations of dietary supplements with survival in the cancer population. However, the associations are small and should be interpreted cautiously due to the variations among different supplements and the small effect size. Future studies should investigate the effect of individual supplements, particularly NVNM supplements, on improving other cancer-related outcomes.

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References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209–249

    Article  PubMed  Google Scholar 

  2. Stein KD, Syrjala KL, Andrykowski MA (2008) Physical and psychological long-term and late effects of cancer. Cancer 112(S11):2577–2592

    Article  PubMed  Google Scholar 

  3. Keene MR, Heslop IM, Sabesan SS, Glass BD (2019) Complementary and alternative medicine use in cancer: a systematic review. Complement Ther Clin Pract 35:33–47

    Article  PubMed  Google Scholar 

  4. Posadzki P, Watson L, Alotaibi A, Ernst E (2012) Prevalence of complementary and alternative medicine-use by UK cancer patients: a systematic review of surveys. J Integr Oncol 1:1

    Google Scholar 

  5. Sanford NN, Sher DJ, Ahn C, Aizer AA, Mahal BA (2019) Prevalence and nondisclosure of complementary and alternative medicine use in patients with cancer and cancer survivors in the United States. JAMA Oncol 5(5):735–737

    Article  PubMed  PubMed Central  Google Scholar 

  6. Velicer CM, Ulrich CM (2008) Vitamin and mineral supplement use among US adults after cancer diagnosis: a systematic review. J Clin Oncol 26(4):665–673

    Article  CAS  PubMed  Google Scholar 

  7. European Food Safety Authority (2018) Food supplements. https://www.efsa.europa.eu/en/topics/topic/food-supplements. Accessed 13 Apr 2022

  8. National Institutes of Health (2018) Dietary supplement health and education Act of 1994 Public Law 103–417. https://ods.od.nih.gov/About/DSHEA_Wording.aspx. Accessed 13 Apr 2022

  9. Kanellopoulou A, Riza E, Samoli E, Benetou V (2021) Dietary supplement use after cancer diagnosis in relation to total mortality, cancer mortality and recurrence: a systematic review and meta-analysis. Nutr Cancer 73(1):16–30

    Article  CAS  PubMed  Google Scholar 

  10. Griffin N, Dowling M (2018) Vitamin D supplementation and clinical outcomes in cancer survivorship. Br J Nurs 27(19):1121–1128

    Article  PubMed  Google Scholar 

  11. Greenlee H, Kwan ML, Kushi LH, Song J, Castillo A, Weltzien E, Quesenberry CP Jr, Caan BJ (2012) Antioxidant supplement use after breast cancer diagnosis and mortality in the life after cancer epidemiology (LACE) cohort. Cancer 118(8):2048–2058

    Article  CAS  PubMed  Google Scholar 

  12. Harris HR, Orsini N, Wolk A (2014) Vitamin C and survival among women with breast cancer: a meta-analysis. Eur J Cancer 50(7):1223–1231

    Article  CAS  PubMed  Google Scholar 

  13. Ambrosone CB, Zirpoli GR, Hutson AD, McCann WE, McCann SE, Barlow WE, Kelly KM, Cannioto R, Sucheston-Campbell LE, Hershman DL (2020) Dietary supplement use during chemotherapy and survival outcomes of patients with breast cancer enrolled in a cooperative group clinical trial (SWOG S0221). J Clin Oncol 38(8):804

    Article  CAS  PubMed  Google Scholar 

  14. Davies AA, Davey Smith G, Harbord R, Bekkering GE, Sterne JA, Beynon R, Thomas S (2006) Nutritional interventions and outcome in patients with cancer or preinvasive lesions: systematic review. J Natl Cancer Inst 98(14):961–973

    Article  PubMed  Google Scholar 

  15. Hamer J, Warner E (2017) Lifestyle modifications for patients with breast cancer to improve prognosis and optimize overall health. CMAJ 189(7):E268–E274

    Article  PubMed  PubMed Central  Google Scholar 

  16. He J, Gu Y, Zhang S (2018) Vitamin A and breast cancer survival: A systematic review and meta-analysis. Clin Breast Cancer 18(6):e1389–e1400

    Article  CAS  PubMed  Google Scholar 

  17. Poole EM, Shu X, Caan BJ, Flatt SW, Holmes MD, Lu W, Kwan ML, Nechuta SJ, Pierce JP, Chen WY (2013) Postdiagnosis supplement use and breast cancer prognosis in the after breast cancer pooling project. Breast Cancer Res Treat 139(2):529–537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Miller MF, Bellizzi KM, Sufian M, Ambs AH, Goldstein MS, Ballard-Barbash R (2008) Dietary supplement use in individuals living with cancer and other chronic conditions: a population-based study. J Am Diet Assoc 108(3):483–494

    Article  PubMed  Google Scholar 

  19. Norman HA, Butrum RR, Feldman E, Heber D, Nixon D, Picciano MF, Rivlin R, Simopoulos A, Wargovich MJ, Weisburger EK (2003) The role of dietary supplements during cancer therapy. J Nutr 133(11):3794S-3799S

    Article  CAS  PubMed  Google Scholar 

  20. Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Bull World Health Organ 85:867–872

    Article  Google Scholar 

  21. Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, Downey P, Elliott P, Green J, Landray M (2015) UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med 12(3):e1001779

    Article  PubMed  PubMed Central  Google Scholar 

  22. UK Biobank (2014) Cancer data: a report on the number of prevalent and incident cases. https://biobank.ctsu.ox.ac.uk/crystal/ukb/docs/cancerpi.pdf. Accessed 13 Apr 2022

  23. Judson PL, Abdallah R, Xiong Y, Ebbert J, Lancaster JM (2017) Complementary and alternative medicine use in individuals presenting for care at a comprehensive cancer center. Integr Cancer Ther 16(1):96–103

    Article  PubMed  Google Scholar 

  24. Bours MJ, Beijer S, Winkels RM, Van Duijnhoven FJ, Mols F, Breedveld-Peters JJ, Kampman E, Weijenberg MP, Van De Poll-Franse LV (2015) Dietary changes and dietary supplement use, and underlying motives for these habits reported by colorectal cancer survivors of the patient reported outcomes following initial treatment and long-term evaluation of survivorship (PROFILES) registry. Br J Nutr 114(2):286–296

    Article  CAS  PubMed  Google Scholar 

  25. Molassiotis A, Fernadez-Ortega P, Pud D, Ozden G, Scott JA, Panteli V, Margulies A, Browall M, Magri M, Selvekerova S (2005) Use of complementary and alternative medicine in cancer patients: a European survey. Ann Oncol 16(4):655–663

    Article  CAS  PubMed  Google Scholar 

  26. John GM, Hershman DL, Falci L, Shi Z, Tsai W-Y, Greenlee H (2016) Complementary and alternative medicine use among US cancer survivors. J Cancer Surviv 10(5):850–864

    Article  PubMed  PubMed Central  Google Scholar 

  27. Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40(5):373–383

    Article  CAS  PubMed  Google Scholar 

  28. Van Buuren S, Groothuis-Oudshoorn K (2011) Mice: multivariate imputation by chained equations in R. J Stat Softw 45:1–67

    Article  Google Scholar 

  29. Azur MJ, Stuart EA, Frangakis C, Leaf PJ (2011) Multiple imputation by chained equations: what is it and how does it work? Int J Methods Psychiatr Res 20(1):40–49

    Article  PubMed  PubMed Central  Google Scholar 

  30. Gnagnarella P, Muzio V, Caini S, Raimondi S, Martinoli C, Chiocca S, Miccolo C, Bossi P, Cortinovis D, Chiaradonna F (2021) Vitamin D supplementation and cancer mortality: narrative review of observational studies and clinical trials. Nutrients 13(9):3285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Keum N, Giovannucci E (2014) Vitamin D supplements and cancer incidence and mortality: a meta-analysis. Br J Cancer 111(5):976–980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ma Y-J, Yu J, Xiao J, Cao B-W (2015) The consumption of omega-3 polyunsaturated fatty acids improves clinical outcomes and prognosis in pancreatic cancer patients: a systematic evaluation. Nutr Cancer 67(1):112–118

    Article  CAS  PubMed  Google Scholar 

  33. Murphy RA, Mourtzakis M, Chu QS, Baracos VE, Reiman T, Mazurak VC (2011) Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer. Cancer 117(16):3774–3780

    Article  CAS  PubMed  Google Scholar 

  34. Chagas TR, Borges D, de Oliveira PF, Mocellin MC, Barbosa AM, Camargo C, Del Moral J, Poli A, Calder P, Trindade E (2017) Oral fish oil positively influences nutritional-inflammatory risk in patients with haematological malignancies during chemotherapy with an impact on long-term survival: a randomized clinical trial. J Hum Nutr Diet 30(6):681–692

    Article  CAS  PubMed  Google Scholar 

  35. Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA (2013) Inflammation-induced cancer: crosstalk between tumors, immune cells and microorganisms. Nat Rev Cancer 13(11):759–771

    Article  CAS  PubMed  Google Scholar 

  36. Tabas I, Glass CK (2013) Anti-inflammatory therapy in chronic disease: challenges and opportunities. Science 339(6116):166–172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Goyal A, Terry MB, Jin Z, Siegel AB (2014) C-reactive protein and colorectal cancer mortality in US adults. Cancer Epidemiol Biomark Prev 23(8):1609–1618

    Article  CAS  Google Scholar 

  38. Zuo H, Ueland PM, Ulvik A, Eussen SJ, Vollset SE, Nygård O, Midttun Ø, Theofylaktopoulou D, Meyer K, Tell GS (2016) Plasma biomarkers of inflammation, the kynurenine pathway, and risks of all-cause, cancer, and cardiovascular disease mortality: the Hordaland health study. Am J Epidemiol 183(4):249–258

    Article  PubMed  PubMed Central  Google Scholar 

  39. van Harten-Gerritsen AS, Balvers MG, Witkamp RF, Kampman E, van Duijnhoven FJ (2015) Vitamin D, inflammation, and colorectal cancer progression: a review of mechanistic studies and future directions for epidemiological studies. Cancer Epidemiol Biomarkers Prev 24(12):1820–1828

    Article  PubMed  Google Scholar 

  40. Alimohammadi M, Rahimi A, Faramarzi F, Golpour M, Jafari-Shakib R, Alizadeh-Navaei R, Rafiei A (2021) Effects of coenzyme Q10 supplementation on inflammation, angiogenesis, and oxidative stress in breast cancer patients: a systematic review and meta-analysis of randomized controlled-trials. Inflammopharmacology 29(3):579–593

    Article  CAS  PubMed  Google Scholar 

  41. Kantor ED, Lampe JW, Vaughan TL, Peters U, Rehm CD, White E (2012) Association between use of specialty dietary supplements and C-reactive protein concentrations. Am J Epidemiol 176(11):1002–1013

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kantor ED, Lampe JW, Navarro SL, Song X, Milne GL, White E (2014) Associations between glucosamine and chondroitin supplement use and biomarkers of systemic inflammation. J Altern Complement Med 20(6):479–485

    Article  PubMed  PubMed Central  Google Scholar 

  43. Dimitriu C, Martignoni M, Bachmann J, Fröhlich B, Tintărescu G, Buliga T, Lică I, Constantinescu G, Beuran M, Friess H (2005) Clinical impact of cachexia on survival and outcome of cancer patients. Rom J Intern Med 43(3–4):173–185

    CAS  PubMed  Google Scholar 

  44. Alok S, Jain SK, Verma A, Kumar M, Mahor A, Sabharwal M (2014) Herbal antioxidant in clinical practice: a review. Asian Pac J Trop Biomed 4(1):78–84

    Article  PubMed  PubMed Central  Google Scholar 

  45. Pawlowska E, Szczepanska J, Blasiak J (2019) Pro-and antioxidant effects of vitamin C in cancer in correspondence to its dietary and pharmacological concentrations. Oxid Med Cell Longev 2019:1–18

    Article  Google Scholar 

  46. UK Biobank (2022) Provisional timeline for future data releases. https://www.ukbiobank.ac.uk/enable-your-research/about-our-data/future-data-release-timelines. Accessed 13 Apr 2022

  47. Mao JJ, Pillai GG, Andrade CJ, Ligibel JA, Basu P, Cohen L, Khan IA, Mustian KM, Puthiyedath R, Dhiman KS (2022) Integrative oncology: addressing the global challenges of cancer prevention and treatment. CA Cancer J Clin 72(2):144–164

    Article  PubMed  Google Scholar 

  48. Yadav K, Lewis RJ (2021) Immortal time bias in observational studies. JAMA 325(7):686–687

    Article  PubMed  Google Scholar 

  49. Fry A, Littlejohns TJ, Sudlow C, Doherty N, Adamska L, Sprosen T, Collins R, Allen NE (2017) Comparison of sociodemographic and health-related characteristics of UK Biobank participants with those of the general population. Am J Epidemiol 186(9):1026–1034

    Article  PubMed  PubMed Central  Google Scholar 

  50. Batty GD, Gale CR, Kivimäki M, Deary IJ, Bell S (2020) Comparison of risk factor associations in UK Biobank against representative, general population based studies with conventional response rates: prospective cohort study and individual participant meta-analysis. BMJ 368:m131

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

research has been conducted using the UK Biobank Resource under Application Number 74158.

Funding

No funding was received for conducting this study.

Author information

Author notes

  1. Vincent Chi-Ho Chung and Yin Ting Cheung have contributed equally and are the co-senior authors.

Authors and Affiliations

  1. School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China

    Chun Sing Lam & Yin Ting Cheung

  2. School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China

    Ho Kee Koon & Vincent Chi-Ho Chung

  3. Department of Clinical Oncology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China

    Herbert Ho-Fung Loong

  4. Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China

    Vincent Chi-Ho Chung

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  1. Chun Sing Lam
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Contributions

CSL: conceptualization; formal analysis; investigation; methodology; writing—original draft; writing—review and editing. HKK: conceptualization; investigation; methodology; writing—original draft; writing—review and editing. HH-FL: conceptualization; methodology; writing—review and editing. VC-HC: conceptualization; methodology; supervision; writing—review and editing. YTC: conceptualization; formal analysis; investigation; methodology; supervision; writing—original draft; writing—review and editing.

Corresponding author

Correspondence to Yin Ting Cheung.

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Conflict of interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Ethical approval

This study was approved by the Survey and Behavioral Research Ethics Committee of the Chinese University of Hong Kong (Reference no. SBRE-21-0310).

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All participants provided written informed consent.

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Lam, C.S., Koon, H.K., Loong, H.HF. et al. Associations of dietary supplement use with all-cause and cause-specific mortality in patients diagnosed with cancer: a large prospective cohort study in the UK Biobank. Eur J Nutr 62, 879–889 (2023). https://doi.org/10.1007/s00394-022-03044-1

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  • DOI: https://doi.org/10.1007/s00394-022-03044-1

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